Trazodone

ID: trazodone

Aliases: trazodone hydrochloride, Desyrel

Type: compound

Route/form: oral prescription tablet

Status: approved_or_labelled

Evidence level: approved / labelled

Best data tier: approved label + human controlled/review

Support scope: human, review/regulatory

Source types: evidence_report, label, meta_analysis, systematic_review

Linked sources: 4

Broad outcomes: Brain / mood / sleep, Cardiovascular / lipids / blood pressure, Hormones / fertility / sexual health

Reading note: These are curation notes anchored to linked sources, not a clinical recommendation or protocol.

Targets / mechanism

• serotonin reuptake inhibition
• 5-HT2 antagonism
• H1/alpha-1 antagonism at sedating exposures

Optimization domains

• depression
• sleep
• insomnia
• anxiety
• serotonin
• cardiovascular
• sexual health

Research basis

• Trazodone is labelled for depression and widely used off-label for sleep because low doses can be sedating through histamine, alpha-1, and serotonergic mechanisms.
• Systematic reviews and sleep-architecture meta-analysis give a real evidence base for the sleep discussion, even if guidelines remain skeptical.
• It belongs in stack analysis because it combines serotonergic, sedating, orthostatic, QT, and rare priapism considerations.

Limits, risks, and missing evidence

• AASM guidance suggests not using trazodone for chronic adult insomnia, reflecting limited benefit certainty relative to alternatives.
• Orthostatic hypotension, next-day impairment, QT risk, serotonin syndrome, and priapism are central constraints.
• Stacking with clomipramine/sertraline, antihistamines, clonidine, beta-blockers, or alcohol-like CNS depressants can compound risk.

Risk flags

• approved drug
• sedating
• serotonergic
• orthostasis
• qt risk
• priapism
• stack interactions

Linked papers, labels, and reviews

1. DailyMed label: trazodone hydrochloride tablet
   label / dailymed_trazodone_label
   Trazodone label covering serotonin syndrome, QT/cardiac arrhythmia risk, orthostatic hypotension/syncope, sedation, and priapism.
2. Clinical Practice Guideline for the Pharmacologic Treatment of Chronic Insomnia in Adults
   evidence_report / pubmed_aasm_insomnia_guideline_2017
   American Academy of Sleep Medicine pharmacologic insomnia guideline; includes recommendations against trazodone and diphenhydramine for chronic adult insomnia.
3. Trazodone changed the polysomnographic sleep architecture in insomnia disorder: a systematic review and meta-analysis
   meta_analysis / nature_trazodone_sleep_architecture_meta_2022
   Systematic review/meta-analysis of trazodone effects on PSG sleep-architecture parameters in insomnia.
4. Trazodone for insomnia: a systematic review
   systematic_review / pubmed_trazodone_insomnia_review_2018
   Systematic review of trazodone insomnia studies; complements AASM guidance and sleep-architecture meta-analysis.